Abstract
Introduction: Advanced gastric cancer or gastroesophageal junction cancer (GC/GEJC) is an aggressive malignancy often having a poor prognosis. Despite current systemic therapies, GC/GEJC remains the third most common cause of cancer-related deaths worldwide. Tislelizumab, an anti-PD1 antibody, has shown promising results in treating various cancers. Therefore, this systematic review investigated the efficacy and safety of tislelizumab plus chemotherapy for patients with GC/GEJC.
Methods: Five databases were systematically searched until July 10, 2024. Articles identified in the screening process included two RCTs based on predefined inclusion criteria. We performed data extraction sheets and quality assessments using the Cochrane ROB2 tool.
Results: Out of the two randomized controlled trials (RCTs), 1646 patients were included in our systematic review. In Rational-306, efficacy outcomes improved, overall survival (OS) significantly improved from 10.6 months (95\% CI 9.3–12.1) to 17.2 months (95\% CI 15.8–20.1), and progression-free survival (PFS) from 5.6 months (4.9–6.0) to 7.3 months (6.9–8.3). Rational-305 also notably significantly improved.
Outcomes: Improved OS from 12.9 months (12.1-14.1) to 15 months (13.6-16.5), and PFS from 6.2 months (5.6 to 6.9) to 6.9 months (5.7 to 7.2). The proportion of patients with any grade 3 or worse treatment-related adverse events was similar between treatment groups.
Conclusion: Compared with chemotherapy and placebo, Tislelizumab plus chemotherapy demonstrates superior efficacy with a similar safety profile in the two groups, encouraging the use of the tislelizumab group in patients with GC/GEJC.
References
1. Zhang S, Orita H, Fukunaga T. Current surgical treatment of esophagogastric junction adenocarcinoma. World J Gastrointest Oncol. 2019: 567 [PMID: 31435459, https://doi.org/10.4251/wjgo.v11.i8.567]
2. Uhlenhopp DJ, Then EO, Sunkara T, Gaduputi V. Epidemiology of esophageal cancer: update in global trends, etiology and risk factors. Clin J Gastroenterol. 2020: 1010 [PMID: 32965635, https://doi.org/10.1007/s12328-020-01237-x]
3. Council C. Oesophageal cancer 2022 [updated 2022]. Available from: https://www.cancer.org.au/cancer-information/types-of-cancer/oesophageal-cancer.
4. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021: 209 [PMID: 33538338, https://doi.org/10.3322/caac.21660]
5. Lerut T, Coosemans W, Decker G, De Leyn P, Nafteux P, Van Raemdonck D. Cancer of the esophagus and gastro-esophageal junction: potentially curative therapies. Surg Oncol. 2001: 113 [PMID: 11750230, https://doi.org/10.1016/s0960-7404(01)00027-5]
6. Abdullah M, Karim AA, Goh KL. Late presentation of esophageal cancer: observations in a multiracial South-East Asian population. J Dig Dis. 2010: 28 [PMID: 20132428, https://doi.org/10.1111/j.1751-2980.2009.00410.x]
7. Ajani JA, Lee J, Sano T, Janjigian YY, Fan D, Song S. Gastric adenocarcinoma. Nat Rev Dis Primers. 2017: 17036 [PMID: 28569272, https://doi.org/10.1038/nrdp.2017.36]
8. Njei B, McCarty TR, Birk JW. Trends in esophageal cancer survival in United States adults from 1973 to 2009: A SEER database analysis. J Gastroenterol Hepatol. 2016: 1141 [PMID: 26749521, https://doi.org/10.1111/jgh.13289]
9. Nowak AK, Lake RA, Marzo AL, Scott B, Heath WR, Collins EJ, Frelinger JA, Robinson BW. Induction of tumor cell apoptosis in vivo increases tumor antigen cross-presentation, cross-priming rather than cross-tolerizing host tumor-specific CD8 T cells. J Immunol. 2003: 4905 [PMID: 12734333, https://doi.org/10.4049/jimmunol.170.10.4905]
10. Lesterhuis WJ, Punt CJ, Hato SV, Eleveld-Trancikova D, Jansen BJ, Nierkens S, Schreibelt G, de Boer A, Van Herpen CM, Kaanders JH, van Krieken JH, Adema GJ, Figdor CG, de Vries IJ. Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice. J Clin Invest. 2011: 3100 [PMID: 21765211, https://doi.org/10.1172/JCI43656]
11. Xu J, Jiang H, Pan Y, Gu K, Cang S, Han L, Shu Y, Li J, Zhao J, Pan H, Luo S, Qin Y, Guo Q, Bai Y, Ling Y, Yang J, Yan Z, Yang L, Tang Y, He Y, Zhang L, Liang X, Niu Z, Zhang J, Mao Y, Guo Y, Peng B, Li Z, Liu Y, Wang Y, Zhou H, Investigators O-. Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial. JAMA. 2023: 2064 [PMID: 38051328, https://doi.org/10.1001/jama.2023.19918]
12. Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017: 2461 [PMID: 28993052, https://doi.org/10.1016/S0140-6736(17)31827-5]
13. Shen L, Guo J, Zhang Q, Pan H, Yuan Y, Bai Y, Liu T, Zhou Q, Zhao J, Shu Y, Huang X, Wang S, Wang J, Zhou A, Ye D, Sun T, Gao Y, Yang S, Wang Z, Li J, Wu YL. Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phase 1/2 study. J Immunother Cancer. 2020: [PMID: 32561638, https://doi.org/10.1136/jitc-2019-000437]
14. Daei Sorkhabi A, ZareDini M, Fazlollahi A, Sarkesh A, Naseri A, Mousavi SE, Nejadghaderi SA, Sullman MJM, Kolahi AA, Safiri S. The safety and efficacy of tislelizumab, alone or in combination with chemotherapy, for the treatment of non-small cell lung cancer: a systematic review of clinical trials. BMC Pulm Med. 2023: 495 [PMID: 38066549, https://doi.org/10.1186/s12890-023-02755-3]
15. Sun H, Bu F, Li L, Zhang X, Xin X, Yan J, Huang T. Efficacy and Safety of Immune Checkpoint Inhibitors Combined With Chemotherapy as First-line Treatment for Recurrent or Metastatic Nasopharyngeal Carcinoma: A Network Meta-analysis of Randomized Controlled Trials. Ann Pharmacother. 2024: 349 [PMID: 37488978, https://doi.org/10.1177/10600280231188171]
16. Qin S, Kudo M, Meyer T, Bai Y, Guo Y, Meng Z, Satoh T, Marino D, Assenat E, Li S, Chen Y, Boisserie F, Abdrashitov R, Finn RS, Vogel A, Zhu AX. Tislelizumab vs Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2023: 1651 [PMID: 37796513, https://doi.org/10.1001/jamaoncol.2023.4003]
17. Quan P, Zhang L, Yang B, Hou H, Wu N, Fan X, Yu C, Zhu H, Feng T, Zhang Y, Qu K, Yang X. Effectiveness and safety of adjuvant treatment of tislelizumab with or without chemotherapy in patients with high-risk upper tract urothelial carcinoma: a retrospective, real-world study. Clin Transl Oncol. 2025: 1221 [PMID: 39172333, https://doi.org/10.1007/s12094-024-03659-2]
18. Desai J, Deva S, Lee JS, Lin CC, Yen CJ, Chao Y, Keam B, Jameson M, Hou MM, Kang YK, Markman B, Lu CH, Rau KM, Lee KH, Horvath L, Friedlander M, Hill A, Sandhu S, Barlow P, Wu CY, Zhang Y, Liang L, Wu J, Paton V, Millward M. Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors. J Immunother Cancer. 2020: [PMID: 32540858, https://doi.org/10.1136/jitc-2019-000453]
19. Xu J, Bai Y, Xu N, Li E, Wang B, Wang J, Li X, Wang X, Yuan X. Tislelizumab Plus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma. Clin Cancer Res. 2020: 4542 [PMID: 32561664, https://doi.org/10.1158/1078-0432.CCR-19-3561]
20. Ajani J, El Hajbi F, Cunningham D, Alsina M, Thuss-Patience P, Scagliotti GV, Van den Eynde M, Kim SB, Kato K, Shen L, Li L, Ding N, Shi J, Barnes G, Van Cutsem E. Tislelizumab versus chemotherapy as second-line treatment for European and North American patients with advanced or metastatic esophageal squamous cell carcinoma: a subgroup analysis of the randomized phase III RATIONALE-302 study. ESMO Open. 2024: 102202 [PMID: 38118368, https://doi.org/10.1016/j.esmoop.2023.102202]
21. Kim SB, Van Cutsem E, Ajani J, Shen L, Barnes G, Ding N, Tao A, Xia T, Zhan L, Kato K. Tislelizumab in advanced/metastatic esophageal squamous cell carcinoma: health-related quality of life in Asian patients. Curr Med Res Opin. 2024: 69 [PMID: 37846080, https://doi.org/10.1080/03007995.2023.2270894]
22. Yan X, Duan H, Ni Y, Zhou Y, Wang X, Qi H, Gong L, Liu H, Tian F, Lu Q, Sun J, Yang E, Zhong D, Wang T, Huang L, Wang J, Chaoyang W, Wang Y, Wan Z, Lei J, Zhao J, Jiang T. Tislelizumab combined with chemotherapy as neoadjuvant therapy for surgically resectable esophageal cancer: A prospective, single-arm, phase II study (TD-NICE). Int J Surg. 2022: 106680 [PMID: 35595021, https://doi.org/10.1016/j.ijsu.2022.106680]
23. Gafton B, Morarasu S, Dimofte G. Role of immunotherapy in gastric cancer with liver metastasis. World J Clin Oncol. 2024: 1383 [PMID: 39582613, https://doi.org/10.5306/wjco.v15.i11.1383]
24. Yan SY, Fan JG. Application of immune checkpoint inhibitors and microsatellite instability in gastric cancer. World J Gastroenterol. 2024: 2734 [PMID: 38899328, https://doi.org/10.3748/wjg.v30.i21.2734]
25. Zhang XM, Yang T, Xu YY, Li BZ, Shen W, Hu WQ, Yan CW, Zong L. Effectiveness and tolerability of programmed cell death protein-1 inhibitor + chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers. World J Gastrointest Oncol. 2024: 1613 [PMID: 38660631, https://doi.org/10.4251/wjgo.v16.i4.1613]

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